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Correction published on 9 June 2016, see Molecules 2016, 21(6), 759.

Open AccessArticle
Molecules 2015, 20(11), 20031-20041; doi:10.3390/molecules201119678

Pharmacokinetics of Ginkgolide B after Oral Administration of Three Different Ginkgolide B Formulations in Beagle Dogs

1
State Key Lab of New-Tech for Chinese Medicine Pharmaceutical Process, Kanion Pharmaceutical Co. Ltd, Lianyungang 222000, Jiangsu, China
2
Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 8 September 2015 / Revised: 27 October 2015 / Accepted: 28 October 2015 / Published: 6 November 2015
(This article belongs to the Section Medicinal Chemistry)
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Abstract

Ginkgolide B (GB), an important active constituent of Ginkgo biloba extract, has been used in clinical applications for the treatment of dementia, cerebral insufficiency or related cognitive decline. To investigate the main pharmacokinetic characteristics of three different GB formulations in beagle dogs, a simple, specific and sensitive LC-MS/MS method was established and validated. The separation of the analytes was achieved on an Agilent Eclipse Plus C18 column (1.8 μm, 2.1 × 50 mm) with a mobile phase consisting of water and acetonitrile. The flow rate was set at 0.4 mL/min. Quantitation was performed using multiple reaction monitoring (MRM) in negative ion mode, with the transitions at m/z (Q1/Q3) 423.1/367.1 for GB and m/z 269.3/170.0 for IS. The linear calibration curve of GB was obtained over the concentration range of 2–200 ng/mL. The intra- and inter-day precisions were <15% and the accuracies were within ±12.7%. The validated method was applied to compare the pharmacokinetic characteristics of GB in healthy beagle dogs after oral administration of three formulations (HME08, GB capsule prepared by hot-melt extrusion technology; LL06, GB pellet prepared by liquid layer technology; conventional GB tablet). The Cmax values of GB from different formulations in beagle dog plasma were 309.2, 192.4 and 66.6 µg/L, and the AUC values were 606.7, 419.1 and 236.2 µg/L·h, respectively. The data suggested that the exposure level of GB from HME08 and LL06 in beagle dog plasma was greatly improved compared with conventional tablets. This study should be helpful for the design and development of oral GB preparations. View Full-Text
Keywords: ginkgolide B; hot-melt extrusion; liquid layer; beagle dog plasma; pharmacokinetics; LC-MS/MS ginkgolide B; hot-melt extrusion; liquid layer; beagle dog plasma; pharmacokinetics; LC-MS/MS
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Zhao, J.; Geng, T.; Wang, Q.; Si, H.; Sun, X.; Guo, Q.; Li, Y.; Huang, W.; Ding, G.; Xiao, W. Pharmacokinetics of Ginkgolide B after Oral Administration of Three Different Ginkgolide B Formulations in Beagle Dogs. Molecules 2015, 20, 20031-20041.

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